Chromogranin A is a low affinity, high capacity Ca2+ binding protein, postulated to be responsible for the IP3-sensitive intracellular Ca2+ store role of secretory vesicles. Contrary to the generally accepted notion that chromogranin A exists as a soluble matrix protein, chromogranin A is now known to interact with the secretory vesicle membrane protein(s) at the intravesicular pH of 5.5. One of the chromogranin A interacting membrane proteins has been identified as the IP3 receptor. It was further shown that four molecules of the intraluminal loop peptide of the IP3 receptor bound to each chromogranin A tetramer, indicating an interaction between the tetrameric IP3 receptor/Ca2+ channel and tetrameric chromogranin A. This represents the first known example of a direct interaction between either an IP3 receptor or a Ca2+ channel and a Ca2+ storage protein. Furthermore, we have purified chromogranin B to complete homogeneity in its native state for the first time from the secretory vesicle lysates. Chromogranin B aggregated much more readily at pH 5.5 than pH 7.5 in the presence of Ca2+, and bound to the vesicle membrane more tightly than chromogranin A. The pH- and Ca2+-induced chromogranin B aggregation is consistent with the proposed roles of chromogranins A and B in vesicle biogenesis. In our current study, we found chromogranin A immunoreactivities in several inner ear cells, thus implicating them not only in Ca2+ controlling roles, but also in secretory roles of the inner ear. Furthermore, the existence of IP3 receptor/Ca2+ channel immunoreactivity in the several inner ear cells has also been found, implying the existence of IP3 receptor-mediated Ca2+ signaling mechanisms in the inner ear.